Dimethyl fumarate modulates the Treg-Th17 cell axis in patients with psoriasis.

BACKGROUND: Dimethyl fumarate (DMF) is the active ingredient of Skilarence™ and Tecfidera™, which are used for the treatment of psoriasis and multiple sclerosis, respectively. Various immunomodulatory mechanisms of action have been identified for DMF; however, it is still unclear what effects DMF exerts in vivo in patients with psoriasis. OBJECTIVES: In this study we examined the effects of DMF, both in vivo and in vitro, on T cells, which play a key role in the pathogenesis of psoriasis. METHODS: The frequency of T-cell subsets was examined by flow cytometry in untreated patients with psoriasis or those treated with DMF. The effects of DMF in vitro on T-cell survival, activation and proliferation, and cell-surface thiols were assessed by flow cytometry. RESULTS: In patients with psoriasis treated with DMF we observed an increase in the frequency of T regulatory (Treg) cells and a decrease in T helper (Th)17 lineage cells and the associated cytokines interleukin-17, interleukin-22 and granulocyte-macrophage colony-stimulating factor. T cells cultured in vitro with DMF exhibited reduced viability, and inhibition of activation and proliferation in response to stimulation due to the oxidative effects of DMF. However, the frequency of Treg cells increased in the presence of DMF due to their heightened ability to resist DMF-induced oxidative stress. CONCLUSIONS: DMF enhanced the ratio of Treg cells to Th17 cells in patients with psoriasis, in patients with multiple sclerosis and in vitro. Furthermore, our data suggest that this is at least in part as a result of the differential effects of DMF on Treg cells compared with conventional T cells.

2017 McDonald diagnostic criteria: A review of the evidence.

The diagnosis of Multiple Sclerosis (MS) has continuously evolved, allowing for an earlier and more accurate diagnosis of MS over time. The McDonald Criteria for diagnosis of MS were originally proposed in 2001, with previous revisions in both 2005 and 2010. The International Panel on Diagnosis in MS have recently reviewed the 2010 McDonald Criteria, and made recommendations for the revised 2017 McDonald Criteria. Any revisions made relied entirely on the available evidence, and not expert opinion. In this review, we provide an overview of the recent 2017 revisions to the McDonald Criteria, focusing in particular on the motivating evidence behind the recommendations made. We also review the existing research around misdiagnosis in MS, as well as areas considered to be high priorities of research, currently lacking in sufficient evidence, which may influence future diagnostic criteria in years to come. Finally, we illustrate some clinical examples, to demonstrate the impact of new diagnostic criteria on time to MS diagnosis in a real-world setting.

Cognitive dysfunction in early multiple sclerosis: a review.

Cognitive impairment is a common and disabling feature of Multiple Sclerosis (MS), including early MS, and may even pre-date any physical symptoms. It contributes even more to withdrawal from work than physical disability. Here, we provide an overview of cognitive impairment in MS, particularly in early MS where it is most commonly under-reported and under-treated. We address the presenting features of CI, its impact on quality of life, and its validated assessments (in particular the use of Brief International Cognitive Assessment in MS for use in a clinical setting). We review the insights radiology has given us into the pathogenesis of cognitive impairment in MS, particularly in early CI and in cognitively preserved MS patients. We review current treatments for cognitive impairment, primarily cognitive rehabilitation. We address the evidence for its associated co-morbidities, which may exacerbate or trigger CI, and should therefore be addressed early in the disease course (smoking, alcohol, mood, fatigue and potential co-existing sleep disorders, exercise, and vitamin D). The article supports the importance for early recognition and management of cognitive impairment in MS, before it becomes an established and irreversible entity.

An unusual presentation of Guillain-Barré syndrome in a young man with bilateral upper extremity weakness.

A 30-year-old man attended the emergency department with a 4-day history of progressive, bilateral upper limb weakness. He had mild shortness of breath and occasional swallowing difficulties. One month prior to presentation, he had flu-like symptoms and diarrhoea. Examination revealed upper limb hypotonia, symmetrical distal arm weakness and hyporeflexia. Power and reflexes in the lower limbs were normal. Nerve conduction studies and lumbar puncture demonstrated features consistent with Guillain-Barré syndrome (GBS). The patient was treated with a 5-day course of intravenous immunoglobulins. He improved significantly over the next 2 weeks. Breathing and swallow function did not deteriorate and required no further intervention. He had a sustained improvement, and remained at baseline 1 year later. Work-up for underlying structural, infectious, inflammatory and paraneoplastic aetiologies were negative. Serum antiganglioside antibodies were positive for the anti-GT1a IgG isotype supporting the clinical diagnosis of the pharyngeal-cervical-brachial variant of GBS.

It is better to be in a clinical trial than not: lessons learnt from clinical neurology--the management of acute multiple sclerosis relapses.

OBJECTIVE: To compare being on-, or off-, a randomized controlled trial (RCT) for the same intervention. DESIGN: Cohort study. SETTING: Ambulatory outpatient clinic in a clinical neurosciences centre. SUBJECTS: Patients experiencing a clinically significant multiple sclerosis (MS) relapse, who received a 3-day regimen of intravenous methylprednisolone as an ambulatory outpatient, were compared with a similar group of patients who had previously been treated exactly in the same way while participating in a RCT. MAIN OUTCOME MEASURES: The Multiple Sclerosis Relapse Management Scale (MSRMS) was used to measure patients' experiences of relapse management in both groups. The two groups were compared under four main headings: interpersonal care, access to care, information and coordination of care. RESULTS: The principal finding was that interpersonal care was significantly worse in the off-trial group (P = 0.0001), implying a beneficial trial effect on patient experience. CONCLUSION: The effect observed is likely secondary to trial participation; both groups had similar baseline features, and were treated in the same way. Likely mechanisms for the differences are protocol, care and Hawthorne effects. The findings support the incorporation of structured RCT-style practice into routine clinical management, in order to deliver a more patient-centred care in the treatment of MS relapses. This may have implications for other chronic neurological diseases.